Neonatal-onset primary mitochondrial disease caused by nuclear gene mutations: a report of 4 cases / 中国新生儿科杂志

Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Association of single nucleotide polymorphisms in the vitamin D receptor gene with the clinical outcome of influenza in children / 中国小儿急救医学

Objective:To investigate the association of single nucleotide polymorphisms(SNPs)in the vitamin D receptor(VDR)gene with influenza susceptibility and severity of disease in children.Methods:Peripheral venous blood was collected from 172 children with influenza A (study group) and 88 healthy children (healthy control group) admitted to Xi ′an Children′s Hospital and Xi ′an Central Hospital from February 2019 to February 2021.Serum 25-hydroxyvitamin D(25-OH-D) level was detected by using 25-OH-D kit.The study group was divided into three groups according to clinical syndrome: mild group, severe group, and critical group.Four candidate loci in the VDR gene(ApaI, TaqI, FokI, and BSMI)were selected, and polymorphisms in the VDR gene of each group were determined by polymerase chain reaction restriction fragment length polymorphism and analyzed in relation to children with influenza.Results:Compared with the healthy control group[(109.65±4.35) nmol/L], the serum 25-OH-D levels in the study groups were lower[(73.55±2.46)nmol/L in the mild group, (45.59±4.62) nmol/L in the severe group, and (33.65±3.87) nmol/L in the critical group]( P<0.05); Genotypes AA, Aa and allele A of the ApaI locus(51.74%, 22.67%, and 63.08%, respectively)and genotypes FF, Ff and allele F of the FokI locus(41.86%, 34.88%, and 59.30%, respectively)accounted for a significantly higher proportion of cases in the study group than those in healthy control group(11.36%, 14.77%, 18.75%, 10.23%, 13.64%, and 17.05%, respectively)( P<0.05). The proportion of allele A at the ApaI locus and genotypes AA and Aa in severe group(63.70%, 43.84%, and 28.76%) were significantly higher than those in mild group(47.37%, 35.09%, and 24.56%)( P<0.05); The proportion of allele A and genotype AA and at the ApaI locus in critical group(92.86%, 88.10%, and 49.52%) were significantly higher than those in severe group( P<0.05). Serum 25-OH-D<50 nmol/L( OR=5.087, 95% CI 3.114-5.648), ApaI site genotypes AA ( OR=4.011, 95% CI 1.217-18.624)and Aa( OR=3.839, 95% CI 2.483-1.456), FokI site genotypes FF( OR=4.112, 95% CI 3.215-20.775)and Ff( OR=4.591, 95% CI 0.032-10.936)were risk factors for the onset of influenza in children. Conclusion:Serum 25-OH-D deficiency is associated with childhood influenza, and VDR gene genotype AA and Aa of ApaI locus, and FokI site genotype FF, Ff may increase the risk of childhood influenza susceptibility, and allele A of ApaI locus and genotypes AA and Aa are associated with the severity of influenza.

Genetic diversity in Mexican wild populations of the Great Curassow (Crax rubra) / Diversidad genética en poblaciones silvestres mexicanas del hocofaisán (Crax rubra)

Abstract The Great Curassow (Crax rubra) is a Neotropical bird with a wide distribution; it is classified under different threat categories and is listed as a vulnerable species by the IUCN. The Official Mexican Standard, the NOM-059-SEMARNAT-2010, indicates that the Great Curassow is a threatened species, and the subspecies Crax rubra griscomi, which is restricted to the island of Cozumel, is classified as critically endangered. Habitat loss and fragmentation, hunting, overexploitation, and illegal trade are among the main factors that have placed the bird at an endangered status. The objective of the present study was to determine the genetic structure and variation of the species within the Mexican populations of Crax rubra by using three mitochondrial markers, and one nuclear marker (COI, ND2, Cyt b, and MUSK). We used 47 samples obtained by noninvasive collection (feathers) including the two different color phases of the female plumage: dark brown and barred (rare in Mexico). Gene flow between the remaining populations is recent and extensive, even between the continental and the island population (C. r. griscomi). The results indicate that the subspecies C. r. rubra and C. r. griscomi do not present a marked genetic differentiation because the second exhibits an exclusive haplotype and a shared haplotype. With this study, we provide the first genetic-geographic approximation of the curassow in Mexico, where a gradual geographic differentiation is observed between the western and eastern populations of the Isthmus of Tehuantepec, and we provide a baseline for future studies. Finally, the information obtained indicates that important genetic diversity persists in the Mexican populations of the Great Curassow and that sufficient conservation within the ecosystems of these subspecies can be obtained by protecting them from overexploitation and by conserving and restoring their habitat.

Resumen El hocofaisán (Crax rubra) es un ave de la región Neotropical con amplia distribución, que se encuentra en diferentes categorías de riesgo, por la IUCN está catalogada como una especie Vulnerable. A nivel nacional, dentro de la NOM-059-SEMARNAT-2010 está considerada como una especie amenazada, y la subespecie Crax rubra griscomi restringida a la isla de Cozumel, está categorizada como en peligro de extinción. Entre los factores principales por los que se encuentra en grave riesgo, destacan la pérdida y fragmentación del hábitat, la cacería, la sobreexplotación, la extracción y el comercio ilegal. El objetivo del presente estudio es conocer la estructura y variación genética de la especie dentro de las poblaciones silvestres mexicanas de Crax rubra, mediante el uso de tres marcadores mitocondriales y uno nuclear (COI, ND2, Cyt b y MUSK). A partir de 47 muestras obtenidas mediante colecta no invasiva (plumas) que incluyen las dos fases de plumaje de la hembra: café oscura y barrada (rara en México). Se observó que el flujo génico entre las poblaciones remanentes es reciente y extenso, incluso entre las poblaciones continentales y la isleña (C. r. griscomi). Los resultados indican que las subespecies C. r. rubra y C. r. griscomi no presentan una marcada diferenciación genética dado que la segunda presentó un haplotipo exclusivo y uno compartido. Con el presente estudio brindamos la primera aproximación genético-geográfica del hocofaisán en México y una línea de base para futuros estudios, en el que se observa una diferenciación geográfica gradual entre las poblaciones del oeste y del este del Istmo de Tehuantepec. Finalmente, la información obtenida indica que en las poblaciones mexicanas del hocofaisán persiste una diversidad genética importante y que su conservación en los ecosistemas puede ser suficiente mediante la protección a la sobreexplotación, la conservación y restauración de su hábitat.

Predominance of Leishmania major and rare occurrence of Leishmania tropica with haplotype variability at the center of Iran

ABSTRACT Background Leishmania major is a causative agent of zoonotic cutaneous leishmaniasis in the center of Iran, Abarkouh district. Molecular characterization and precise incrimination of Leishmania species was carried out to perform controlling measurements and to design treatment programs for zoonotic cutaneous leishmaniasis. Methods All smears isolated from ulcers of suspected patients were examined under a light microscope and graded for amastigotes frequency. Extraction of DNA, PCR, RFLP and sequencing of ITS-rDNA genotype were done to increase the efficacy of Leishmania parasites identification at their species-specific level and to detect any Leishmania infections within. Results Humans were found to be infected with L. major with high infection frequency and also Leishmania tropica was identified with low occurrence for the first time as non-native species using molecular analyses. The rates of infections was considerable with microscopic observation (n= 65, 73%) out of 89 smears prepared from suspected patients. Molecular analyses showed that the density of L. major was significantly higher (n= 48, 53.93%) than L. tropica (n= 4, 4.49%) (Mann-Whitney U test: p< 0.05) and two samples (2.25%) remained ambiguous after several sequencing. L. major did not have diversity with two common haplotypes but L. tropica were found to exhibit high diversity with three novel haplotypes. Conclusion L. major was considered the causative agent of leishmaniasis in the region, but the identification of a non-native L. tropica revealed the importance of further isolation of Leishmania parasites following molecular analyses and confirmation, and also revealed the importance of further isolation of Leishmania parasites from patients of the field areas who do not have easily access to health care centers for specialized treatment strategies.